Clinical Trials Register

Summary
EudraCT Number:	2023-000005-12
Sponsor's Protocol Code Number:	CRCFC-TEICO.SA.2022
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2023-01-30
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2023-000005-12

A.3

Full title of the trial

An open-label study to evaluate the safety and tolerability of inhaled Teicoplanin in the treatment of Staphylococcus aureus (including mrsa) infections in CYSTIC FIBROSIS PATIENTS

Studio in aperto per valutare la sicurezza e la tollerabilità della teicoplanina inalata nel trattamento delle infezioni da Staphylococcus aureus (incluso MRSA) nei pazienti con fibrosi cistica

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

An open-label study to evaluate the safety and tolerability of inhaled Teicoplanin in the treatment of Staphylococcus aureus (including mrsa) infections in CYSTIC FIBROSIS PATIENTS

Studio in aperto per valutare la sicurezza e la tollerabilità della teicoplanina inalata nel trattamento delle infezioni da Staphylococcus aureus (incluso MRSA) nei pazienti con fibrosi cistica

A.3.2

Name or abbreviated title of the trial where available

study to evaluate the safety of inhaled Teicoplanin in the treatment of Stafilococco infections

Studio per valutare sicurezza della teicoplanina inalata nelle infezioni da Stafilococco

A.4.1

Sponsor's protocol code number

CRCFC-TEICO.SA.2022

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AZIENDA OSPEDALIERA UNIVERSITARIA INTEGRATA VERONA
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Azienda Ospedaliera Universitaria Integrata Verona
B.5.2	Functional name of contact point	UOC Fibrosi Cistica
B.5.3	Address:
B.5.3.1	Street Address	P.le Stefani, 1
B.5.3.2	Town/ city	Verona
B.5.3.3	Post code	37126
B.5.3.4	Country	Italy
B.5.4	Telephone number	0458122293
B.5.6	E-mail	marco.cipolli@aovr.veneto.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	TEICOPLANINA SANDOZ - 200 MG POLVERE E SOLVENTE PER SOLUZIONE INIETTABILE O INFUSIONE 1 FLACONCINO VETRO DA 200 MG E 1 FIALA VETRO DA 3 ML
D.2.1.1.2	Name of the Marketing Authorisation holder	SANDOZ S.P.A.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/17/1913
D.3 Description of the IMP
D.3.1	Product name	Teicoplanina Sandoz 200 mg
D.3.2	Product code	[Teicoplanina 200 mg]
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	TEICOPLANINA
D.3.9.1	CAS number	61036-62-2
D.3.9.2	Current sponsor code	Teicoplanina
D.3.9.4	EV Substance Code	SUB04714MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	200
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

cystic fibrosis associated to persistent Staphylococcus aureus (including MRSA) infection

fibrosi cistica e infezione persistente da Staphylococcus aureus (incluso MRSA)

E.1.1.1

Medical condition in easily understood language

cystic fibrosis associated to persistent Staphylococcus aureus (including MRSA) infection

fibrosi cistica e infezione persistente da Staphylococcus aureus (incluso MRSA)

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10011762
E.1.2	Term	Cystic fibrosis
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10075981
E.1.2	Term	Staphylococcus aureus infection
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to determine the safety and tolerability of inhaled teicoplanin in patients suffering from cystic fibrosis associated to persistent Staphylococcus aureus (including MRSA) infection treated with the drug at a dosage of 200 mg/3ml BID for two cycles of 28 days separated by 28 days without treatment.

L'obiettivo primario dello studio è determinare la sicurezza e la tollerabilità della teicoplanina per via inalatoria in pazienti affetti da fibrosi cistica associata ad infezione persistente da Staphylococcus aureus (incluso MRSA) trattati con il farmaco alla dose di 200 mg/3ml BID per due cicli di 28 giorni separati da 28 giorni senza trattamento

E.2.2

Secondary objectives of the trial

• to assess the degree of microbiological improvement following treatment with inhaled teicoplanin at a dosage of 200 mg/3ml BID for two cycles of 28 days separated by 28 days without treatment, measured as reduction of the Staphylococcus aureus CFUs presence in the sputum throughout the study period.
• to assess the effect of the treatment with inhaled teicoplanin on the FEV1 value, in comparison to baseline.
• to assess the effect of the treatment with inhaled teicoplanin on the Lung Clearance Index (LCI) value, in comparison to baseline.
• to assess the effect of the treatment with inhaled teicoplanin on the plethysmography values, in comparison to baseline.
• to evaluate the effect of the treatment with inhaled teicoplanin in eradicating persistent Staphylococcus aureus infection.

• valutare il grado di miglioramento microbiologico dopo il trattamento con teicoplanina per via inalatoria alla dose di 200 mg/3 ml BID per due cicli di 28 giorni separati da 28 giorni senza trattamento, misurato come riduzione della presenza di CFU di Staphylococcus aureus nell'espettorato durante tutto lo studio periodo.
• valutare l'effetto del trattamento con teicoplanina sul valore del FEV1, rispetto al basale;
• valutare l'effetto del trattamento con teicoplanina sul valore dell'indice di clearance polmonare (LCI), rispetto al basale.
• valutare l'effetto del trattamento con teicoplanina sui valori pletismografici, rispetto al basale.
• valutare l'effetto del trattamento con teicoplanina nell'eradicazione dell'infezione persistente da Staphylococcus aureus.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female patients, aged =12 years with a confirmed diagnosis of cystic fibrosis and persistent Staphylococcus aureus (including MRSA) infection (=3 positive culture of Staphylococcus aureus (including MRSA) in sputum within the 24 months prior to enrollment).
2. Patients with FEV1 = 50% and = 90% of predicted.
3. Patients able to understand the nature of the study and willing to comply with the protocol requirements.
4. Patients who (or if < 18 years of age, whose guardians) have signed written informed consent to participate to the study after benefits and risks have been fully explained.

1. Pazienti di sesso maschile o femminile, di età = 12 anni con diagnosi confermata di fibrosi cistica e infezione persistente da Staphylococcus aureus (incluso MRSA) (=3 colture positive di Staphylococcus aureus (incluso MRSA) nell'espettorato nei 24 mesi precedenti l'arruolamento).
2. Pazienti con FEV1 = 50% e = 90% del predetto.
3. Pazienti in grado di comprendere la natura dello studio e disposti a rispettare i requisiti del protocollo.
4. Pazienti che hanno firmato il consenso informato scritto a partecipare allo studio dopo che benefici e rischi sono stati completamente spiegati.

E.4

Principal exclusion criteria

1. Patients with Pseudomonas aeruginosa chronic infection.
2. Patients under treatment with Kaftrio+Kalydeco for less than 6 consecutive months.
3. Patients with medical history of hemoptysis (> 300 cc in 30 days).
4. Patients with decreased liver function (AST or ALT > 3 times higher in comparison to reference values).
5. Inability to tolerate inhaled products.
6. Patients with renal insufficiency.
7. Patients lung transplanted and on the waiting list for lung transplantation.
8. Patients with known or suspected allergy or hypersensitivity to glycopeptides or other antibiotics.
9. Patients treated with nebulized or systemic vancomycin or teicoplanin within 8 weeks before the study enrollment.
10. Patients with known episodes of bronchoconstriction after drug inhalation.
11. Abnormal laboratory findings or other findings or medical history at Screening that, in the Investigator's opinion, would compromise the safety of the subject or the quality of the study data.
12. Patients who are participating or have participated in other clinical studies within the 30 days before the study enrollment.
13. Female patients who are pregnant or breast-feeding or who wish to become pregnant during the period of the clinical study and for one months later.
14. Female patients of childbearing age (less than 24 months after the last menstrual cycle) who do not use adequate contraception.

1. Pazienti con infezione cronica da Pseudomonas aeruginosa.
2. Pazienti in trattamento con Kaftrio+Kalydeco per meno di 6 mesi consecutivi.
3. Pazienti con anamnesi di emottisi (> 300 cc in 30 giorni).
4. Pazienti con funzionalità epatica ridotta (AST o ALT > 3 volte superiori rispetto ai valori di riferimento).
5. Pazienti con incapacità di tollerare i prodotti inalati.
6. Pazienti con insufficienza renale.
7. Pazienti trapiantati di polmone e in lista d'attesa per il trapianto di polmone.
8. Pazienti con allergia o ipersensibilità nota o sospetta ai glicopeptidi o ad altri antibiotici.
9. Pazienti trattati con vancomicina o teicoplanina nebulizzata o sistemica entro 8 settimane prima dell'arruolamento nello studio.
10. Pazienti con episodi noti di broncocostrizione dopo inalazione di farmaci.
11. Risultati di laboratorio anormali o altri risultati o anamnesi allo Screening che, secondo l'opinione dello Sperimentatore, comprometterebbero la sicurezza del soggetto o la qualità dei dati dello studio.
12. Pazienti che partecipano o hanno partecipato ad altri studi clinici nei 30 giorni precedenti l'arruolamento nello studio.
13. Pazienti di sesso femminile in gravidanza o allattamento o che desiderano una gravidanza durante il periodo dello studio clinico e per un mese successivo.
14. Pazienti di sesso femminile in età fertile (meno di 24 mesi dopo l'ultimo ciclo mestruale) che non usano una contraccezione adeguata.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of the study is the evaluation of safety and tolerability to inhaled teicoplanin in patients suffering from cystic fibrosis associated to persistent Staphylococcus aureus (including MRSA) infection treated with the drug at a dosage of 200 mg/3ml BID for two cycles of 28 days separated by 28 days without treatment. This will be measured as: a) decline from baseline of FEV1 value = 20% after 30 minutes from administration; b) oxygen saturation < 90% after 30 minutes from administration; c) severe coughing; d) chest tightness; e) throat discomfort; f) moderate/severe dyspnea.

L'endpoint primario dello studio è la valutazione della sicurezza e tollerabilità della teicoplanina per via inalatoria in pazienti affetti da fibrosi cistica associata a infezione persistente da Staphylococcus aureus (incluso MRSA) trattati con il farmaco alla dose di 200 mg/3 ml BID per due cicli di 28 giorni separati da 28 giorni senza trattamento. Questo sarà misurato come: a) declino dal basale del valore FEV1 = 20% dopo 30 minuti dalla somministrazione; b) saturazione di ossigeno < 90% dopo 30 minuti dalla somministrazione; c) forte tosse; d) oppressione toracica; e) fastidio alla gola; f) dispnea moderata/grave.

E.5.1.1

Timepoint(s) of evaluation of this end point

30 minutes from administration

dopo 30 minuti dalla somministrazione

E.5.2

Secondary end point(s)

Changes in bacterial load of Staphylococcus aureus in sputum as determined by CFU at baseline (Visit 2) and at Visits 5 (after 1st treatment cycle), 6 (after 2nd treatment cycle) and 9/10 (at End of Study, after follow-up period), in comparison to baseline.; Changes in pulmonary function tests as determined by FEV1 at baseline (Visit 2) and at each study visit until End of Study, in comparison to baseline.; Changes in Lung Clearance Index (LCI) measured at baseline (Visit 2) and at each study visit until End of Study, in comparison to baseline.; Changes in plethysmography values measured at baseline (Visit 2) and at the end of the treatment (Visit 5); Rate of persistent Staphylococcus aureus infection eradication among the patients being treated with the drug at a dosage of 200 mg/3ml BID for two cycles of 28 days separated by 28 days without treatment.

Variazioni della carica batterica di Staphylococcus aureus nell'espettorato come determinato da CFU al basale (Visita 2) e alle Visite 5 (dopo il 1° ciclo di trattamento), 6 (dopo il 2° ciclo di trattamento) e 9/10 (alla fine dello studio, dopo il follow- periodo up), rispetto al basale.; Cambiamenti nei test di funzionalità polmonare determinati dal FEV1 al basale (Visita 2) e ad ogni visita dello studio fino alla fine dello studio, rispetto al basale.; Variazioni dell'indice di clearance polmonare (LCI) misurate al basale (Visita 2) e ad ogni visita dello studio fino alla fine dello studio, rispetto al basale.; Variazioni dei valori pletismografici misurati al basale (Visita 2) e alla fine del trattamento (Visita 5); Tasso di eradicazione persistente dell'infezione da Staphylococcus aureus tra i pazienti trattati con il farmaco alla dose di 200 mg/3 ml BID per due cicli di 28 giorni separati da 28 giorni senza trattamento.

E.5.2.1

Timepoint(s) of evaluation of this end point

at baseline (Visit 2) and at Visits 5 (after 1st treatment cycle), 6 (after 2nd treatment cycle) and 9/10 (at End of Study, after follow-up period), in comparison to baseline.; at baseline (Visit 2) and at each study visit until End of Study, in comparison to baseline.; at baseline (Visit 2) and at each study visit until End of Study, in comparison to baseline.; at baseline (Visit 2) and at the end of the treatment (Visit 5); end of study

al basale (Visita 2) e alle Visite 5 (dopo il 1° ciclo di trattamento), 6 (dopo il 2° ciclo di trattamento) e 9/10 (alla fine dello studio, dopo il follow- periodo up), rispetto al basale.; al basale (Visita 2) e ad ogni visita dello studio fino alla fine dello studio, rispetto al basale.; al basale (Visita 2) e ad ogni visita dello studio fino alla fine dello studio, rispetto al basale.; al basale (Visita 2) e alla fine del trattamento (Visita 5); fine studio

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

underage patients

Pazienti minorenni

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

best practice

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2023-09-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2024-02-21

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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